Genetic Variant TAFA2:p.Arg4Lys (chr12-61867415-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_178539.5(TAFA2):c.11G>A(p.Arg4Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000719 in 1,391,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TAFA2
NM_178539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

Publications

0 publications found

Variant links:

Genes affected

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. [provided by RefSeq, Jul 2008]

TAFA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30953237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA2	NM_178539.5 link	c.11G>A	p.Arg4Lys	missense_variant	Exon 2 of 5	ENST00000416284.8	NP_848634.1	Q8N3H0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA2	ENST00000416284.8 link	c.11G>A	p.Arg4Lys	missense_variant	Exon 2 of 5	1	NM_178539.5	ENSP00000393987.3		Q8N3H0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391388

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31472

American (AMR)

AF:

0.00

AC:

AN:

42420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25492

East Asian (EAS)

AF:

0.00

AC:

AN:

39242

South Asian (SAS)

AF:

0.00

AC:

AN:

82666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1053640

Other (OTH)

AF:

0.00

AC:

AN:

57948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.11G>A (p.R4K) alteration is located in exon 2 (coding exon 1) of the FAM19A2 gene. This alteration results from a G to A substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T;.;T;.;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

.;T;T;T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.31

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;L;.;.;.;.

PhyloP100

5.6

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.61

N;N;D;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.031

D;D;D;D;T;T

Sift4G

Uncertain

0.013

D;D;D;.;D;.

Polyphen

0.18

B;B;.;.;.;.

Vest4

0.48

MutPred

0.23

Gain of methylation at R4 (P = 0.0158);Gain of methylation at R4 (P = 0.0158);Gain of methylation at R4 (P = 0.0158);.;.;.;

MVP

0.39

MPC

0.67

ClinPred

0.86

GERP RS

6.1

Varity_R

0.24

gMVP

0.46

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over